ElAzzouny Mahmoud, Tom Christopher T M B, Evans Charles R, Olson Lori L, Tanga Mary J, Gallagher Katherine A, Martin Brent R, Burant Charles F
From the Departments of Internal Medicine.
Chemistry, and.
J Biol Chem. 2017 Mar 24;292(12):4766-4769. doi: 10.1074/jbc.C117.775270. Epub 2017 Feb 10.
Itaconic acid is an important metabolite produced by macrophages after stimulation with LPS. The role of itaconate in the inflammatory cascade is unclear. Here we used [C]itaconate and dimethyl [C]itaconate (DMI) to probe itaconate metabolism, and find that [C]DMI is not metabolized to itaconate. [C]Itaconate in the cell culture medium leads to elevated intracellular levels of unlabeled succinate, with no evidence of intracellular uptake. The goal of this study is to encourage the development of effective pro-drug strategies to increase the intracellular levels of itaconate, which will enable more conclusive analysis of its action on macrophages and other cell and tissue types.
衣康酸是巨噬细胞在受到脂多糖刺激后产生的一种重要代谢产物。衣康酸盐在炎症级联反应中的作用尚不清楚。在这里，我们使用[C]衣康酸盐和二甲基[C]衣康酸盐（DMI）来探究衣康酸盐的代谢，发现[C]DMI不会代谢为衣康酸盐。细胞培养基中的[C]衣康酸盐会导致细胞内未标记琥珀酸盐水平升高，且没有细胞内摄取的证据。本研究的目的是鼓励开发有效的前药策略，以提高细胞内衣康酸盐的水平，从而能够更确凿地分析其对巨噬细胞以及其他细胞和组织类型的作用。
